SIRT6, a New Hope in Liver Diseases: From Pathogenic Mechanisms to Therapeutic Strategies.

Abstract

The liver is a vital organ in the human body, responsible for multiple functions, including immunity, digestion, detoxification, and vitamin storage. Liver diseases cause approximately 2 million deaths annually, accounting for 4% of global mortality, making it a worldwide health challenge. The NAD⁷-dependent deacetylase SIRT6 plays a crucial role in key physiological and pathological processes of liver diseases. With an emphasis on its regulatory mechanisms in lipid metabolism, inflammatory responses, oxidative stress, and various liver diseases, this review summarizes the multifaceted role of SIRT6 in hepatic physiology and pathology. SIRT6 maintains hepatic lipid homeostasis and regulates hepatic inflammation and oxidative stress via multiple signaling pathways, thereby alleviating liver diseases such as liver fibrosis, NAFLD, and liver cancer. The study also discusses how natural and chemical activators, such as MDL- 800 and diosgenin, can activate SIRT6 or upregulate its expression, thereby improving liver damage. Consequently, SIRT6 represents a promising therapeutic target for the development of novel strategies against liver disorders.